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Biomedical subjects

D Douer

Publications and source records attributed to D Douer.

At least 73 records · Page 4Linked to original sources

Circulating pluripotent haemopoietic cells in patients with myeloproliferative disorders.

Peripheral blood cells of 17 patients with myeloproliferative disorders were grown in vitro to form mixed colonies (CFU-mix). CFU-mix were found in four of nine patients with chronic phase chronic myelocytic leukaemia (CML) at levels 28- to 132-fold higher than the upper limits of normal subjects. These patients also had higher than normal levels of circulating granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitors. Development of blastic crisis was associated with disappearance of CFU-mix from the blood. CFU-mix was detected in the blood of three of five patients with polycythaemia vera (PV) and two patients with myelofibrosis with myeloid metaplasia (MMM) at levels slightly higher than those of normal subjects. Our results are consistent with a clonal expansion of multipotent haematopoietic precursor cells in CML and abnormal kinetics of this cell in CML, PV and MMM.

Adult↗

Retinoic acid. Inhibition of the clonal growth of human myeloid leukemia cells.

Vitamin A and its analogues (retinoids) affect normal and malignant hematopoietic cells. We examined the effect of retinoids on the clonal growth in vitro of myeloid leukemia cells. Retinoic acid inhibited the clonal growth of the KG-1, acute myeloblastic leukemia, and the HL-60, acute promyelocytic leukemia, human cell lines. The KG-1 cells were extremely sensitive to retinoic acid, with 50% of the colonies inhibited by 2.4-nM concentrations of the drug. A 50% growth inhibition of HL-60 was achieved by 25 nM retinoic acid. Complete inhibition of growth of both leukemia cell lines was seen with 1 microM retinoic acid. Exposure of KG-1 cells to retinoic acid for only 3-5 d was sufficient to inhibit all clonal growth. The all-trans and 13-cis forms of retinoic acid were equally effective in inhibiting proliferation. Retinal, retinyl acetate, and retinol (vitamin A) were less potent inhibitors. Clonal growth of the human K562 and mouse M-1 myeloid leukemic cell lines was not affected by 10 microM retinoic acid. Retinoic acid also inhibited the clonal growth of leukemia cells from five of seven patients with acute myeloid leukemia. Retinoic acid at concentrations of 5 nM to 0.3 microM inhibited 50% clonal growth, and 1 microM retinoic acid inhibited 64-98% of the leukemic colonies. The inhibition of clonal growth of KG-1 and HL-60 cell lines and of leukemic cells from two patients was not associated with the presence of a specific cytoplasmic retinoic acid-binding protein. Our study suggests that retinoic acid may prove to be effective in the treatment of human myeloid leukemia.

Animals↗

Retinoic acid enhances growth of human early erythroid progenitor cells in vitro.

We studied the effect of retinoic acid on the clonal proliferation of normal human early erythroid progenitor cells in vitro. Normal peripheral blood cells were cultured in methylcellulose with erythropoietin and the number of burst-forming units-erythroid (BFU-E) colonies were scored on day 12 of culture. All-trans retinoic acid increased the number of colonies in a dose-response fashion. Maximal stimulation occurred at 30 nM retinoic acid, which increased the number of BFU-E by a mean of 225 +/- 25% (+/- SE) over plates containing erythropoietin alone. Colony formation increased even in the presence of maximally stimulating concentrations of erythropoietin. The 13-cis retinoic acid stimulated BFU-E proliferation in a parallel manner as the trans analogue, while retinol (vitamin A) did not affect clonal growth. This data supports further the thesis that retinoic acid, in addition to its known effect on epithelial cells, may be involved in the growth of normal hematopoietic cells.

Cell Differentiation↗

Cryopreservation of the human multipotent stem cell.

Light density human bone marrow cells were cryopreserved, then thawed and tested for their ability to form myeloid (CFUGM), erythroid (BFUE) and mixed myeloid-erythroid colonies in vitro. Proliferation of mixed hematopoietic colonies was supported by conditioned media from a human T-lymphocyte cell line and erythropoietin. All mixed colonies contained neutrophil and erythroid precursors and approximately 25% had mononuclear phagocytes. Following cryopreservation the bone marrow retained its capacity to form mixed colonies without apparent loss. The recovery of CFUGM and BFUE was 76% and 72% respectively.

Bone Marrow↗

High-dose combined-modality therapy and autologous bone marrow transplantation in resistant cancer.

Fourteen patients with resistant cancers received high-dose chemotherapy and total body irradiation followed by rescue with autologous cryopreserved bone marrow cells. In seven patients, disease has remained in remission for periods up to two years. These data indicate that effectiveness of high-dose combined-modality therapy and bone marrow autotransplantation in patients with resistant cancer. The high incidence of non-marrow toxicity may be reduced by the use of this modality before patients have received extensive therapy.

Adolescent↗

Chronic myelocytic leukaemia: a pluripotent haemopoietic cell is involved in the malignant clone.

Haemopoietic cells with pluripotent capabilities, were grown in soft-gel cultures from the peripheral blood of a glucose-6-phosphate dehydrogenase (G6PD) electrophoretic A,B heterozygous female with chronic myelocytic and granulocytic progeny. Only type B isoenzyme of G6PD was found in mixed colonies, in mature neutrophils, erythrocytes, and committed granulocyte and isoenzymes of G6PD. This study provides direct evidence that a pluripotent haemopoietic stem cell is involved in the malignant clone in CML.

Adult↗

Serum immunoglobulin levels in splenectomized Hodgkin patients and in subjects following post-traumatic splenectomy.

Mean serum immunoglobulin levels (IgG, IgA, IgM) in splenectomized Hodgkin's disease patients in remission were compared with a control group of splenectomized healthy subjects following trauma. The controls showed a higher IgA and lower IgM than the normal. The IgM of the Hodgkin's group were decreased below the normal but showed no difference from the control group. IgA and IgG levels were not significantly different from the levels in the splenectomized healthy subjects. These results suggest that changes in immunoglobulins in splenectomized Hodgkin patients could be attributed to the effect of the removal of the spleen.

Adolescent↗

Hemochromatosis in a renal transplant recipient.

A 47 year old kidney transplant recipient who died from liver failure caused by hemochromatosis, is described. The diagnosis was established by post mortem examination. The question whether these findings are an extreme form of the common pathological changes seen in the liver in other transplant recipients, or were related to infectious hepatitis or were due to the use of immunosuppressive therapy, remains unanswered.

Female↗

Depressed PHA transformation and acute leukemia in macroglobulinemia.

Two out of fifty-three patients with macroglobulinemia developed acute leukemia following chemotherapy. The Phytohemagglutinin (PHA) Transformation Index performed prior to the appearance of acute leukemia was found to be markedly depressed in these two patients in comparison with ten other patients with macroglobulinemia. In addition, a clone with monosomy 7 was detected in one of the currently reported patients when the leukemic process became apparent. The cytogenetic analysis was normal in the same patient 48 months earlier, when macroglobulinemia was diagnosed. The low PHA Transformation Index and the chromosomal hypodiploidy are of interest and their clinical significance merits further investigation.

Adolescent↗

Benign cholestatic jaundice after nephrectomy for pyonephrosis and sepsis.

Severe benign postoperative intrahepatic cholestatic jaundice appeared immediately after nephrectomy in a patient with nephrolithiasis and septicemia. Convalescence was uneventful and no treatment was necessary. This diagnostic possibility should be considered whenever jaundice appears postoperatively for pyonephrosis and septicemia.

Cholestasis↗